MEDICAL HYPOTHESES AND RESEARCH
VOL. 1, No. 1, January 2005


D. Wang, et al. [2005] Med Hypotheses Res 2: 295-302.

Protective Effect of Pregnenolone Sulfate Against
Scopolamine-induced Memory Impairment in an
Experimental Animal Model


Dan Wang, Rong Yu* and Ying-Qing Lu

Department of Pharmacology, Shanghai Medical College, Fudan University, Shanghai
200032, China


Abstract. Aim: To investigate the effect of pregnenolone sulfate (PS) on
scopolamine-induced memory impairment in mice and also to probe the possible
mechanisms of its action. Methods: In all experiments, the pharmacological model of
amnesia in mice was induced by i.p. administration of scopolamine (1 mg/kg). The
number of errors and the latency in the step-down task and the latency in the
step-through task were measured 24 hours after the training. The activity of
acetylcholinesterase (AChE) and choline O-acetyltransferase (ChAT) was also measured in
the cortex and hippocampus 24 hours following drug administration. Results: In the
step-down task experiments, scopolamine increased the step-down number of errors (P <
0.05) and reduced the step-down latency (P < 0.01). Pretreatment with PS (1 mg/kg, s.c.)
reduced scopalamine-induced step-down errors (P < 0.05), and it also reversed a decrease
in the step-down latency (P < 0.05). In the step-through task experiments, while
scopolamine reduced the step-through latency (P < 0.01), pretreatment with PS (1 mg/kg,
s.c.) reversed the decrease (P < 0.01). In addition, scopolamine administration increased
the AChE activity and decreased the ChAT activity in the cortex and hippocampus, but
pretreatment with PS (1 mg/kg, s.c.) significantly diminished the effects of scopolamine on
the activity of AChE and ChAT in the brain. Conclusion: Administration of PS partially
protected against the memory impairment in mice induced by scopolamine. The
mechanisms of this protective effect likely relate to an inhibition of the AChE activity and
an increase of the ChAT activity in the cortex and hippocampus.

*Address all correspondence to: Dr. Rong Yu, Department of Pharmacology, Shanghai
Medical College, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, China.
Phone: 86-21-5423-7228.  E-mail:
ryu@shmu.edu.cn


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